No unified immunophenotypic profiles and corresponding analytic strategies have been established for the rapid diagnosis of acute promyelocytic leukemia (APL) using flow cytometry (FCM). Here we describe a characteristic immunophenotypic panel that can rapidly and accurately distinguish APL from other types of adult acute myeloid leukemia (AML) using only FCM. By comparing APL cells and non-APL AML cells that share APL common immunophenotypes (CD34−CD117+HLA−DR−) we found that CD64 was a significant factor that differentiated APL from other AMLs. Further retrospective analyses of 205 APL and 629 non-APL AML patients from different hematology centers showed that either the CD64dim and homoCD13+homo CD33+homoMPO+ (myeloperoxidase) CD11c− panel or the CD64dim and homoCD13+homo CD33+homoMPO+ CD11c+CD10−CD117+ SSChigh (high side scatter signal) panel could distinguish APL from non-APL AML patients with nearly 100% sensitivity, specificity and accuracy. Moreover, relative quantification of CD64 expression enhanced the applicability of our APL diagnostic immunophenotypic panels (ADI-panels) in different hematology centers. Application of the ADI-panels will decrease diagnosis time and improve personalized treatment for APL, a life-threatening disease with very rapid progression.
Background
Several studies have used CD157 in white blood cells with or without proaerolysin (fluorescein‐labeled proaerolysin [FLAER])‐based flow cytometry assays in the diagnosis of paroxysmal nocturnal hemoglobinuria (PNH).
Methods
We designed a seven‐color CD marker panel comprising FLAER, CD15, CD64, CD24, CD14, CD157, and CD45 to verify CD157's clinical applicability and diagnostic performance in a clinical setting.
Results
A total of 356 samples were tested. These included 43 PNH‐positive samples and 313 PNH‐negative samples. PNH clones confirmed by the CD157/FLAER combination were almost identical in size to the clones detected by the CD24/CD14/FLAER combination, and the accuracy of the CD157/FLAER combination was 100% in granulocytes and 99.7% in monocytes. Substitution of FLAER with CD157 resulted in 1.9% and 3.5% false‐positives in granulocytes and monocytes, respectively. The accuracy was 98.3% and 96.9% in granulocytes and monocytes, respectively. Moreover, the loss of CD157 expression in granulocytes and monocytes was commonly observed in non‐PNH patients. Some monocytes in non‐PNH patients had weak expression of CD14 but normal expression of FLAER. In this study, PNH clones in granulocytes were always lower than those in matched monocytes.
Conclusions
We performed the first prospective exploration of the clinical usefulness of FLAER and CD157 in simultaneously recognizing PNH clones in granulocytes and monocytes and verified the applicability of CD157 in substitute for both CD14 and CD24. In the conditions where FLAER is not available, substitution of FLAER with CD157 is acceptable for the identification of PNH clones under the premise of giving full attention to the potential for false‐positives.
Background
The MRD status detected using multiparameter flow cytometry (MFC) before allogeneic hematopoietic stem cell transplantation (allo‐HSCT) has crucial prognostic value for patients with acute myeloid leukemia (AML) in morphologic complete remission (CR). We designed a novel panel of antibodies to identify aberrant differentiation/maturation profiles of residual leukemia cells in patients who were not diagnosed at our institution, relapsed with an antigenic shift, or lack leukemia‐associated immunophenotypes.
Methods
We compared the MRD status detected using MFC and real‐time quantitative polymerase chain reaction (RT‐qPCR) in the same 158 bone marrow samples collected from 44 AML patients carrying leukemia‐specific fusion genes. The clinical performance of the MFC‐based MRD status was analyzed in 168 AML patients who exhibited morphologic CR (135) or active disease (33) before HSCT.
Results
Strong concordance was found between MFC‐based and RT‐qPCR‐based MRD status (κ = 0.868). Among the patients displaying CR, the positive MRD status detected using MFC was correlated with a worse prognosis [HRs (P values) for relapse, event‐free survival, and overall survival: 4.83 (<0.001), 2.23 (0.003), and 1.79 (0.049), respectively]; the prognosis was similar to patients with an active disease before HSCT. Patients with a positive MRD before HSCT might experience a benefit from developing chronic graft‐vs‐host disease.
Conclusions
The assessment of MRD using our self‐built different‐from‐normal AML‐MRD detection panel exhibited reliable sensitivity, specificity, and accuracy. In addition, patients with a positive MRD status before transplantation may have higher risk of relapse and worse survival.
Background: The translocation t(12; 22) (p13;q12) is a recurrent but infrequent chromosome abnormality in human myeloid malignancies. To date, the role of TEL-MN1 fusion in leukemogenic process and drug resistance is still largely unknown. Methods: In the present study, the TEL-MN1 fusion was transfected into HL-60 cells to upregulate TEL-MN1 expression via a retroviral vector. MTT assay was employed to examine cell viability and flow cytometry was performed to evaluate cell apoptosis. Idarubicin was used to treat HL-60 cells for estimating the effect of TEL-MN1 fusion on the chemotherapy resistance. Results: The results showed that overexpression of TEL-MN1 in HL-60 cells could promote cell proliferation, suggesting that TEL-MN1 may be involved in the leukemogenesis process. HL-60 cells treated with idarubicin showed a weakened cell viability, whereas TEL-MN1 overexpression attenuated the idarubicin-induced inhibition of cell viability and acceleration of cell apoptosis of HL-60 cells. Conclusion: Taken together, our results indicated that TEL-MN1 fusion is an oncogene involved in the leukemogenesis process and TEL-MN1 overexpression enhanced resistance of HL-60 cells to idarubicin, which may provide a useful tool for studying the mechanism of leukemogenesis and drug resistance.
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